The main objectives of this project are to determine the effects of compounds using two well-established paradigms: (1) drug discrimination and (2) self-administration. Two distinct experimental protocols, pretreatment and substitution, may be conducted within each paradigm. In the drug discrimination paradigm, male rhesus monkeys will be trained to discriminate an intramuscular injection of cocaine from saline. Subsequently, coded compounds will be studied by determining whether selected doses, administered pre-session, reduce the discriminative-stimulus effects of cocaine (pretreatment) and/or whether selective doses of the compound itself can produce cocaine-like effects (substitution). In the drug self-administration paradigm, Mm will be prepared with indwelling IV catheters, and trained to self-administer IV cocain in daily sessions that also include food self-administration components. Each coded compound will be tested in Mm in which the dose-response function for IV cocaine self-administration has been determined. In the pretreatment protocol, tests will be conducted, first, to identify a pretreatment dose that reduces self-administration of the peak reinforcing unit dose of IV cocaine without greatly altering food self-administration, and second, to determine how that dose alters the cocaine dose response function for IV self-administration. In the substitution protocol, selected unit doses of the coded compound will be made available of IV self-administration to evaluate their reinforcing effects. Follow-up studies may be conducted with promising compounds.